Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI

Lin Chen, Zhiliang Wei, Kannie W.Y. Chan, Shuhui Cai, Guanshu Liu, Hanzhang Lu, Philip Chun Wong, Peter C Van Zijl, Tong Li, Jiadi Xu

Research output: Contribution to journalArticle

Abstract

The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (−3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (ΔST) by subtracting the Z-spectral signals at ±3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at ±3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the ΔST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution ΔST images of AD mouse brains at ±3.6 ppm of mouse brains showed significantly reduced ΔST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.

Original languageEnglish (US)
Pages (from-to)380-390
Number of pages11
JournalNeuroImage
Volume188
DOIs
StatePublished - Mar 1 2019

Keywords

  • Alzheimer's disease (AD)
  • Chemical exchange saturation transfer (CEST)
  • Magnetization transfer contrast (MTC)
  • Radial acquisition
  • Saturation transfer (ST)
  • UTE-CEST

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

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